CREAM, OINTMENT & LOTION
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Double-blind
Study
PHARMACEUTICAL LIQUIDS

There are couples of factors that we need to consider to prepare a liquid pharmaceutical product.
These factors directly determine the patient acceptance and compliance to the products.

There are over 9000 taste buds in our tongue, which distinguish salty, bitter, sweet and sour
tastes. Drugs which dissolve in solution directly contact and stimulate these taste buds. Since
most of the drugs taste bitter, palatability becomes  a major concern in developing an oral liquid
product. Palatability means the property of being acceptable to the mouth. It is affected by a
combination of sensory perceptions such as taste, smell, texture, appearance and temperature of
the products. We can "make our products" become appearing, if we optimize these factors.

Low molecular weight salts usually taste salty, higher molecular weight salts and compounds
containing nitrogen usually taste bitter. Organic compounds containing hydroxyl groups tend to be
sweet. And, their sweetness increases, as the number of OH group increases. Esters, alcohols
and aldehydes have pleasant taste and cool sensation.

Altering taste perception by masking unpleasant tastes with a flavoring agent is a common way to
produce palatable products. Cinnamon, raspberry, orange, maple, butterscotch, glycyrrhiza syrup
are commonly used to mask the salty taste of oral liquid medications. Fruit, berry and vanilla are
widely used to mask the sweetness of the medications. Cocoa, chocolate-mint, wild cherry,
walnut and raspberry syrup are usually used to mask the bitter taste of the drug. Finally, fruit,
citrus and cherry syrup are typically used to mask the sour taste.

Other ways to improve the palatability of the product include manupulation of the product odor,
temperature and texture. The scent of any oral solution should be pleasant, and correlate with its
flavor. Cold drinks generally reduces unpleasant taste. Patients may loss their
"medication-appetites", if they find a big chunk of undissolved solid in their oral liquid solution.
Appearance of the products is very important. Clear, water-like solutions may be poorly accepted,
as patients may think that it is lack of potency. Dark color such as black, dark purple and brown
may also be rejected, as patients may think that it contains poisons. Patients generally accept
fruity and more pleasant colors.

When we formulate an oral liquid solution, we also need to consider the age of the patients.
Children generally prefer sweet, fruity and candy-like tastes while elderly may prefer mint or even
wine flavored vehicles.

Finally, when we formulate a liquid product, we should also consider its texture, i.e. viscosity.
Some patients may think that a less-viscous-solution is lack of potency (ie, not enough drug
inside the solution) while more-viscous solution is unpleasant.

PHARMACEUTICAL LOTIONS

INTRODUCTION

Lotions are usually liquid suspensions or dispersions. They consist of finely powdered, insoluble
solids held in more or less permanent suspension by the presence of suspending agents and/or
surfactants. Calamine Lotion (USP) is the classic example of this type of preparation. It can be
prepared by triturating the ingredients into a smooth paste and then adding the remaining liquid
phase. This procedure can be done manually by using pestle and mortar. However, high shear
mixer or homogenizer can often produce a better dispersion.

EXAMPLES OF LOTIONS

Calamine Lotion
Composition: calamine 8 g, zinc oxide 8 g, glycerin 2 mL, Avicel R Gel 2 g, carboxymethylcellulose
(CMC) 2 g and calcium hydroxide solution about 50 mL.
Procedure
(1) Disperse Avicel R into 55 g of water to form a gel,
(2) Mix the calamine, zinc oxide with the glycerin, the gel and the CMC,
(3) Add sufficient amount of calcium hydroxide solution to make the final volume of 100 mL.

Hydrocortisone Lotion
Composition: hydrocortisone 10 g, chlorocresol 0.5 g, self-emulsifying monostearin 40 g, glycerol
63 g and purified water approximately 1000 g.
Preparation:
(1) Dissolve the chlorocresol in 850 mL of  warm water,
(2) Add the self-emulsifying monostearin and heat the mixture to 60C, stir constantly.
(3) Trituate the hydrocortisone with the glycerol and incorporate it to the solution, stir constantly.
(4)  Add purified water to make the final weight of 1000 g, after the mixture cools down.

OINTMENTS AND CREAMS

INTRODUCTION

Ointments are used topically as protectants, antiseptics, emollients, antipruritics, kerotolytics and
astringents. The ointment base is very important, as it determines the use of the ointment. An
ointment base which can penetrate into the skin and release the medication is an ideal base for
antiseptic ointment, while an ointment base has a "poor pentrating power" is ideal for
a protective ointment against moisture, air, UV lights and other external factors.

OINTMENT BASES

Ointment bases are divided into five types and they are oleaginous bases, absorption bases,
water-in-oil emulsion bases, oil-in-water emulsion bases and water-miscible bases. Each type
of the ointment bases has its unique physical characteristics and here is the summary:

Oleaginous Ointment Bases-composed of oleaginous compounds, low water content,
hydrophobic, diffcult to be spreaded and washed, mainly used as protectants and emollients.
Examples are white petrolatrum and white ointment.

Absorption Ointment Bases (I)-composed of oleaginous base and a surfactant, low water
content, hydrophilic, diffcult to be spreaded and washed, mainly used as protectants and
emollients. Examples are hydrophilic petrolatum, anhydrous lanolin, Aquabase, Aquaphor and
Polysorb.

Water-in-oil Emulsion Ointment Bases (II)-composed of oleaginous base, a small amount of
water and a surfactant, high water content, hydrophilic, easy to be spreaded but difficult to be
washed, mainly used as emollients and cleansing creams. Examples are cold creams, hydrous
lanolin, rose water ointment, Hydrocream, Eucerin and Nivea.

Oil-in-water Emulsion Ointment Bases (III)-composed of oleginous base, a large amount of water
and a surfactant, high water content, hydrophilic, easy be spreaded and washed, mainly used as
emollients and drug carriers. Examples are hydrophilic ointment, Dermabase, Velvachol and
Unibase.

Water-miscible Ointment Bases (IV)-composed of polyethylene glycols, hydrophilic, easy be
spreaded and washed, mainly used as drug carriers. Examples are PEG Ointment and Polybase.

PREPARATION

Oleaginous Base (White Ointment)
Composition: white wax 5% and white petrolatum 95%.
Procedure: Melt the white wax, add the petrolatum, stir the mixture till liquefied. Stop heating, stir
the mixture till it begins to congeal.

Absorption Base
Compostion: cholesterol 3%, stearyl alcohol 3%, white wax 8% and white petrolatum 86%
Procedure: Melt the stearyl alcohol, white wax and petrolatum together. Add the cholesterol to the
mixture, stir until completely dissolved. Stop heating, stir the mixture till it begins to congeal.

Water-in-oil Emulsion Base (Cold Cream)
Composition: white wax 12.0%, cetyl esters wax 12.5%, mineral oil (Sp. Gr. = 0.9) 56.0%, sodium
borate 0.5% and 19% water.

Procedure:    Melt the white wax and cetyl esters wax at 70C, add the mineral oil. Dissolve borate
in water to form borate solution, heat the solution to 70C. Add the solution to the oil mixture, stir.
Keep stirring till it hegains to congeal.

Oil-in-water Emulsion Base (Hydrophilic Ointment)
Composition:  Sodium lauryl sulfate (SLS) 1.0%, propylene glycol (PG; SP Gr = 1.035) 12%,
stearyl alchohol 25.0%, white petrolatum 25.0%, purified water 37.0%
Procedure: Melt the stearyl alcohol and white petrolatum at 70C----oil phase. Dissolve SLS and
PG in water, and heat the mixture to 70C--aqueous phase. Add the oil phase slowly to the
aqueous phase, stir. Stop heating, stir till it begains to congeal.

Water Miscible Base
Composition: Polyethylene glycol 400 (PEG) 60% and polyethylene glycol 3350 (PEG 3350) 40%.
Procedure:  Melt the PEGs to 65C. Stir till the mixture congeals.

HOW TO CONVERT THESE OINTMENTS INTO DRUG CARRIERS

The way to incorporate the drug substance into the ointment base depends on the drug solubility
in the ointment base or the phase.

Oleaginous Base
Insoluble drug: Mix the drug with a small amount of mineral oil (levigating agent) to form a
homogenous phase. And then, mix this "wetted powder" into the base with an amount
of ointment of approximately the same size. Then, add and mix a second amount of ointment
approximately equal to the first mixture. Continue this  stepwise "dilution process" (or
geometric dilution) till all of the ointment has been used.
Soluble drug: Melt the base and then add the drug to the molten base (fusion method). Stop
heating and stir till it congeals.

Absorption Base
Methods to incorporate drugs in oleaginous base can also be applied here. However, one more
method can be used here: dissolve water-soluble drug in a small amount of water first and then
mix the aqueous phase with base mechanically. Heat the mixture, if neccessary.

Water-in-oil Emulsion Base
Drug soluble in the oil phase: Levigate the drug with mineral oil, combine it with the oil phase and
then, mix it with the aqueous phase.
Water-soluble drug: Dissolve the drug in the aqueous phsae first. Then, combine it with the oil
phase.

Oil-in-water Emulsion Base
Water-soluble drug: Dissolve the drug in the aqueous phsae first. Then, combine it with the oil
phase.

Drug soluble in the oil phase: Levigate the drug with mineral oil, combine it with the oil phase and
then, mix it with the aqueous phase.

Water Miscible Base
Water-soluble drug: Dissolve the water-soluble drug in a small amount of water and incorporate it
into    the base.

Water-insoluble drug: Levigate the insoluble powder with a water miscible material such as
glycerin; propylene glycol or PEG 400. And then, incorporate this mixture into the base.



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